Pyrotinib dimaleate

Pyrotinib dimaleate (SHR-1258 dimaleate) is a potent and selective EGFR/HER2 dual inhibitor with IC₅₀s of 13 and 38 nM, respectively^[1]. IC50 & Target: IC50: 13 nM (EGFR), 38 nM (HER-2)^[1] In Vitro: Pyrotinib dimaleate has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). Pyrotinib dimaleate inhibits BT474 and SK-OV-3 cells with IC₅₀s of 5.1 and 43 nM, respectively. Pyrotinib dimaleate displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC₅₀ of 790 nM, and others >3000 nM)^[1]. In Vivo: Pyrotinib dimaleate has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib dimaleate has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects (oral; t_1/2=15 h) with a much longer half life than that of preclinical animal species such as mouse (i.v.; t_1/2=1.56 h; i.g.; t_1/2=2.52 h) and rat (i.v.; t_1/2=4.42 h; i.g.; t_1/2=3.38 h)^[1].